Post radical prostatectomy (RP) PSA outcomes following 6 vs 18 months of perioperative androgen deprivation therapy (ADT) in men with localized high risk prostate cancer (LHRPC): Results of Part 2 of a randomized phase 2 trial.
Authors: Rana R. McKay, Wanling Xie, Xiaoyu Yang, Dana E. Rathkopf, Vincent Paul Laudone, Glenn Bubley, David Johnson Einstein, Peter Chang, Andrew Wagner, Christopher J. Kane, J. Kellogg Parsons, Mark A. Preston, Kerry L. Kilbridge, Steven Lee Chang, Atish Dipankar Choudhury, Quoc-Dien Trinh, Mark Pomerantz, Adam S. Kibel, Mary Ellen Taplin
Journal: Journal of Clinical Oncology (2023)

5095 Background: Patients with LHRPC have an increased risk of relapse following RP. We previously reported on Part 1 of a phase 2 trial testing neoadjuvant apalutamide, leuprolide, and abiraterone acetate plus prednisone (ALAAP) or leuprolide and abiraterone plus prednisone (LAP) for 6 months followed by RP (McKay, J Urol, 2021). We demonstrated favorable pathologic responses (tumor &lt;5 mm) at RP in 20.3% of patients (n=24/118). Herein, we report the results of Part 2 testing adjuvant ALAAP (NCT02903368). Methods: Eligible patients had a Gleason score ≥4+3, PSA &gt;20 ng/mL, or T3 disease (by DRE or MRI) and lymph nodes &lt;20 mm. At Part 2, patients were randomized 1:1 to ALAAP for 12 months (Arm 2A) or observation (Arm 2B), stratified by neoadjuvant therapy and pathologic T stage (&lt;ypT3 or ≥ypT3). The primary endpoint was biochemical progression-free survival (bPFS) at 3 years post-RP. bPFS was defined as the time from randomization to progression (PSA ≥ 0.2 ng/mL, local/distant disease on CT/MRI or bone scan, or receipt of post-RP therapy or radiation for rising PSA) or death. The Kaplan-Meier estimate of bPFS at 3 years was compared between arms using a Chi-square test (Klein, Stat Med, 2007). Secondary endpoints included safety and time to testosterone recovery (&gt;200 ng/dL). Results: Overall, 82/118 (69%) of patients enrolled to Part 1 were randomized to Part 2. Median follow-up was 47 months post-RP. Patient preference was the main reason for non-randomization in Part 2. In the intent-to-treat analysis, the 3-year bPFS estimate was 80% (95% CI:65-90%) for Arm 2A and 72% (95% CI:56-84%) for Arm 2B, which was not statistically significant (2-sided p=0.39). Patients who achieved pathologic responses (n=14) had longer bPFS than non-responders (log-rank test two-sided p=0.03; 3-year bPFS 100% vs 72%). In per-protocol population, of 36 patients receiving Arm 2A treatment with available data, 83% had testosterone recovery and median time to recovery from therapy end was 8.7 months. For patients on observation (n=42), 95% had testosterone recovery, and median time to recovery from RP was 4.0 months. No new safety signals were observed. Conclusions: Neoadjuvant ADT in LHRPC resulted in favorable pathologic responses and 3-year bPFS in a subset of patients. As 30% of patients declined an additional 12 months of adjuvant treatment, the study was underpowered to detect a difference between 6 months vs. 18 months of treatment. Subsequent analyses will evaluate predictors of improved bPFS. Clinical trial information: NCT02903368 . [Table: see text]